This invention pertains to a practical and economical process for the production of mercaptoalkanedicarboxylic acids and esters of the same. In a particular aspect this invention concerns the production of thiomalic acid and its esters.
Conventionally, mercaptoalkanedicarboxylic acid esters have been prepared by esterification of the corresponding acid, and hence their availability and manufacture have depended on the availability and manufacture of the mercaptoalkanedicarboxylic acid. While mercaptoalkanedicarboxylic acids have been known for many years, they have never reached large volume industrial production and have remained high cost products.
The simplest mercaptoalkanedicarboxylic acid, thiomalic acid or 2-mercaptobutanedioic acid, is a polyfunctional compound which undergoes the typical reactions of mercaptans and dicarboxylic acids. It is used in the pharmaceutical field, particularly with heavy metals where the sodium salt is less toxic than 2,3-dimercaptopropanol and more effective against poisoning by bismuth, mercury, or arsenic. Thiomalic acid has been reported to reduce the color of crepe rubber and to tackify butadiene type synthetic rubber as disclosed by W. Sharkey in U.S. Pat. No. 2,449,418 of Sept. 14, 1948. Esters of thiomalic acid have been disclosed as air hardening coating compounds by B. Pratt in U.S. Pat. No. 2,456,314 of Dec. 14, 1948 and as ingredients and reactants for the preparation of organotin mercaptocarboxylic acid ester stabilizer compositions for polyvinyl chloride by E. Weinberg in U.S. Pat. Nos. 2,648,650 of Aug. 11, 1953 and 2,832,752 of Apr. 29, 1958; by G. P. Mack in U.S. Pat. No. 2,914,506 of Nov. 24, 1959 and by L. R. Brecker in U.S. Pat. Nos. 3,642,848 of Feb. 15, 1972 and 3,674,737 of July 4, 1972.
Methods heretofore proposed for the production of thiomalic acid are not generally suited for commercial scale operations, primarily because of the poor yields they afford and the length of the reaction period required. Furthermore, yields in actual practice have been found to vary substantially even though the process conditions are most carefully controlled, and this is due to the fact that the thiomalic acid is highly soluble in water and partition coefficients against extracting solvents are unfavorable. With several extractions needed during its recovery, much thiomalic acid can therefore be oxidized to undesirable by-products.
Thiomalic acid may be prepared from maleic acid and hydrogen sulfide in a variety of ways. In British Pat. No. 670,702 the method is described using maleic acid and sodium hydrosulfide in the presence of sodium hydroxide. The sodium hydrosulfide should be prepared by using hydrogen sulfide and an excess of sodium hydroxide as is well known in the literature.
According to EXAMPLE 1 in the above British Patent, the preparation of thiomalic acid, it takes a considerable amount of time, 191/2 hours, and the resulting acidification of the reaction mixture to give crude thiomalic acid gives only about 35% yield of the crude acid based on the maleic acid charged. Concentration of the mother liquors is necessary to give an additional 38% of product. It is then necessary to recrystallize from water and then from ethyl acetate to purify the thiomalic acid. No finished yield is given in this example although it was shown that a 87% yield of mercaptan had been formed in the solution by titration. It has been found in practice that the actual yield of thiomalic acid after going through the concentration of mother liquors, recrystallization etc., is of a lower order, approximately 25-30%. The large loss in yield is due to the similar solubilities of thiomalic acid and by product sodium chloride both in water and in ethyl acetate. It is also necessary to recrystallize the product due to the impurities formed such as the disulfides and other compounds such as the thioether thiodisuccinic acid, and inorganic salts.
The reaction of hydrogen sulfide with esters of maleic acid and with maleic anhydride are also known, but these reactions take a completely different course. As disclosed by L. Newton in U.S. Pat. No. 2,603,616 of July 15, 1952, hydrogen sulfide and an alkene 1,2-dicarboxylic ester such as dibutyl maleate react smoothly in the presence of a tertiary amine catalyst to give tetrabutyl 2,2'-thiodisuccinate, a thioether ester rather than a mercaptan derivative. Newton indicates that at best a small quantity of mercaptoalkanedicarboxylic acid ester might have been obtainable by this reaction since the reaction of mercaptoalkanedicarboxylic ester with alkenedicarboxylic acid ester is more rapid than the reaction of the latter with hydrogen sulfide. F. Zienty in Journal of Organic Chemistry, Vol. 27 (1962) page 3144 stated that "Maleic anhydride does not react with hydrogen sulfide in benzene solution in the absence of a basic catalyst; the solution remains colorless and the maleic anhydride is recovered unchanged. With base present in catalytic amounts, reaction with maleic anhydride occurs as rapidly as hydrogen sulfide is introduced to the reaction mixture. Under a variety of conditions and ratios of reactants the product obtained is in every case the adduct of two moles of maleic anhydride and one of hydrogen sulfide. There is no evidence that the reaction can be interrupted at the 1:1 addition stage".
Another synthesis for forming thiomalic acid is by the reaction of thioacetic acid and maleic acid as cited in Flett and Garner's, "Maleic Anhydride Derivatives", (J. Wiley, New York 1952) page 225. The example given here uses thioacetic acid plus maleic acid to give mercaptosuccinic acid acetate having the formula ##STR1## and the yield is 83% of that required by theory for the latter but no yield is given for the subsequent alkaline hydrolysis of this acetate to disodium thiomalate and sodium acetate and the eventual acidification to give thiomalic acid. This procedure is impractical in that the thioacetic acid preparation is expensive and is not commercially available on a large scale at an economical price, and thus is a drawback to this process. Moreover, once thiomalic acid is obtained by alkaline hydrolysis of the acetate and acidification, it must still be isolated from the water solution containing inorganic salts, just as in the sulfide process of the British patent already discussed.
As discussed above the sulfide procedure is uneconomical because of low yield and the necessity to remove by-products by recrystallization in solvents, which are expensive and cause hazards. At least some of these difficulties apply equally to the thioacetic acid procedure.
At present time there is a need for a commercial process that is economical for preparing thiomalic acid and its esters so that many valuable industrial products can be made.
My process overcomes the numerous disadvantages among which is the fact that the processes are inconvenient or dependent on expensive intermediates to prepare thiomalic acid or esters.